Weight management while taking antipsychotics: two semaglutide trials

The short answer

Two trials found greater weight loss with semaglutide than placebo in people with schizophrenia taking antipsychotic medication. They studied weight management alongside psychiatric care—not a replacement for that care.

HISTORI: 30 weeks in Denmark

This trial enrolled 154 adults with schizophrenia, prediabetes, and a BMI of at least 27. Participants received weekly semaglutide, increased to 1 mg, or placebo.

Average weight changed by −9.04 kg with semaglutide versus +0.17 kg with placebo. Blood-sugar control was the main outcome; weight was a secondary outcome.

Digestive symptoms were more frequent with semaglutide. More repeat hospital admissions occurred in that group, concentrated among a few participants. Psychiatric symptom scores did not clearly differ.

COaST: 36 weeks in Australia

Thirty-one adults taking clozapine received weekly semaglutide, increased to 2 mg, or placebo. Average weight loss was 13.88% versus 0.42%.

Researchers found no clear difference in measured clozapine levels or psychosis scores. However, recruitment stopped short of the planned 80 participants because study medication became unavailable.

What to take away

These findings support further study of weight-management options for people often excluded from larger trials. Neither trial establishes long-term psychiatric safety. Do not compare their weight figures directly: the participants, doses, timeframes, and units differed.

HISTORI received foundation and regional support, with medication supplied by Novo Nordisk. COaST reported public and health-service funding without pharmaceutical-industry support.